Phospholipase C isozymes in the human brain and their changes in Alzheimer's disease.
Phosphoinositide-specific phospholipase C is a key enzyme in signal transduction. We have previously demonstrated that an isozyme of phospholipase C, phospholipase C-delta1, accumulates aberrantly in the brains of patients with Alzheimer's disease. In the present study, we examined the property of phospholipase C isozymes in human brains using the methods of chromatofocusing and gel filtration chromatography, and investigated their changes in Alzheimer's disease brains. The chromatofocusing profile of human brain phospholipase C activity on a Mono P HR column demonstrated that phospholipase C-gamma1, exhibiting an isoelectric point value of 5.2, and phospholipase C-delta1, exhibiting isoelectric point values of 5.2 and 4.6, are partly overlapped in their elution. In contrast, the elution profiles of control and Alzheimer's disease brain phospholipase C on Superdex 200 pg column gel filtration chromatography indicated that phospholipase C-gamma1 and phospholipase C-delta1 can be separated with the elution position having a molecular weight of about 240,000 and 140,000, respectively, in the human brain. Using this gel filtration chromatography it was revealed that the phospholipase C-gamma1 activity was significantly decreased and the phospholipase C-delta1 activity was significantly increased in Alzheimer's disease brains compared with controls. These results suggest that the phospholipase C isozymes are differentially involved in Alzheimer's disease.
Shimohama
S
S
Department of Neurology, Faculty of Medicine, Kyoto University, Sakyoku, Japan.
Sasaki
Y
Y
Fujimoto
S
S
Kamiya
S
S
Taniguchi
T
T
Takenawa
T
T
Kimura
J
J
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002845:Chromatography; D002850:Chromatography, Gel; D006801:Humans; D007120:Immunochemistry; D007527:Isoenzymes / Q000737:chemistry*; D008970:Molecular Weight; D010738:Type C Phospholipases / Q000737:chemistry*
D007527:Isoenzymes; D010738:Type C Phospholipases